DESCRIPTION: (Applicant's Abstract) The purpose of the proposed research is to examine the neurobiology of nicotine reinforcement and dependence. In humans, nicotine addiction with its inherent health consequences is a far-reaching societal problem. Nicotine has been shown to be a reinforcer with animals self-administering intravenous nicotine. An animal model of nicotine withdrawal has been established based on the appearance of somatic symptoms following the removal of nicotine. Preliminary studies have indicated that this withdrawal syndrome is also characterized by a negative affective state reflected in elevated ICSS reward thresholds. The neurochemical substrates of nicotine reinforcement assessed by intravenous nicotine self-administration will be examined after the administration of various nicotinic antagonists. Progressive augmentation to repeated withdrawals will be investigated using the ICSS reward threshold procedure and somatic symptoms. Further, the effects of repeated withdrawals on acute nicotine reinforcement will be examined using the self-administration procedure. Finally, the role of specific brain sites which may mediate the affective and somatic aspects of nicotine withdrawal will be investigated. Characterization of the neurobiology of nicotine reinforcement and withdrawal in rats will provide information critical to the prevention and treatment of nicotine dependence and drug addiction in general.